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Delayed hypokalemic paralysis following a convulsion due to alcohol abstinence
Journal of Clinical Neuroscience 13 (2006) 453–456 www.elsevier.com/locate/jocn
Clinical study
Delayed hypokalemic paralysis following a convulsion due to alcohol abstinence Wei-Hsi Chen, Hsin-Ling Yin, Hung-Sheng Lin, Shun-Sheng Chen, Jia-Shou Liu
*
Department of Neurology, Chang Gung Memorial Hospital, 100 Tai Pei Road, Niao Sung Hsiang, Kaohsiung 833, Taiwan Received 16 September 2004; accepted 7 April 2005
Abstract We encountered three patients with hypokalemic paralysis following a convulsion in the early stages of alcohol abstinence. The transtubular potassium gradient was less than 2.0, suggesting intracellular potassium shift. Hypokalaemic paralysis may result from retention of intracellular cationic potassium bound by anionic phosphorylated compounds, precipitated by an acceleration of the Na+–K+ pump in alcohol withdrawal and convulsions. These findings warn of the lethal hypokalemia that may occur after convulsions, particularly soon after alcohol abstinence associated with moderate withdrawal symptoms. Ó 2006 Elsevier Ltd. All rights reserved. Keywords: Hypokalaemic paralysis; Alcohol; Convulsion; Potassium; Catecholamine
1. Introduction
2. Patients and methods
Hypokalaemic paralysis is a disorder characterized by skeletal muscle weakness due to an intracellular shift of extracellular potassium. Primary hypokalaemia is a channelopathy due to a gene mutation with an incidence of 1 in 100 000.1 However, some conditions can provoke hypokalaemic paralysis secondarily. Hyperthyroidism and hyperaldosteronism are the leading causes in Asian and Caucasian populations, respectively.2 Other causes include licorice ingestion, barium poisoning, renal tubular acidosis, diuretic abuse, Bartter syndrome, gastroenteritis and villous adenoma of the colon.1 Total body potassium does not change in primary hypokalaemic paralysis or thyrotoxic periodic paralysis, whereas in secondary disorders it is depleted via the renal or alimentary routes. Hypokalaemic paralysis has not been reported as a postictal complication previously. We report three patients with postictal hypokalemic paralysis soon after alcohol abstinence and discuss the underlying physiological mechanisms.
We treated three men with concomitant acute paraparesis and hypokalaemia following their first-ever tonic–clonic seizure, 5–7 days after alcohol abstinence. They were heavy drinkers for 2–10 years, compatible with chronic alcoholism and alcoholic dependence according to DSM-IV criteria.3 Needle electromyogram, serum potassium (K) and transtubular potassium gradient (TTKG) were performed during the paralysis, and serum K was repeated after recovery. Serum biochemistry, trace element survey, haematology, immunology, serology, toxicology (alcohol, benzodiazepine, amphetamine, heroin), urinalysis, neuroendocrinology, arterial and urine gas analysis, glucoseinsulin loading test, thyrotropin-releasing hormone test, abdominal sonography, cranial computerised tomography (CT), adrenal CT, electroencephalogram, nerve conduction studies and liver sonography were performed to investigate possible causes of the hypokalemic paralysis and to evaluate the extent of alcohol damage. Glucose-insulin loading (100 g glucose initially and 200 g again if no response) and thyrotropin-releasing hormone tests were performed 1 week after the convulsion. The formula used to determine TTKG was (Kurine/Kplasma)/(Osmurine/Osmplasma). A non-
*
Corresponding author. Tel.: +886 7 312 1101; fax: +886 7 323 4237. E-mail address: [email protected] (J.-S. Liu).
0967-5868/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.jocn.2005.04.032
454
W.-H. Chen et al. / Journal of Clinical Neuroscience 13 (2006) 453–456
renal cause is considered when TTKG is less than two, whereas a TTKG over five indicates an increased net secretion of potassium in the cortical collecting ducts (hypokalaemia). 3. Results The three men suffered a moderate alcohol withdrawal reaction after abstinence. There was no history of high carbohydrate intake, high calorie diet, or alcoholic consumption prior to the convulsion. They denied recent head injury, migraine, consumption of drugs or herbs, or a family history of seizures or paralysis. In all patients, the glucose-insulin loading test, thyrotropin-releasing hormone test, electroencephalogram and adrenal sonography and CT were normal. Liver sonography showed fatty liver and cirrhosis. Needle electromyogram showed no resting potential during paraparesis. 3.1. Case 1 This 55-year-old man had consumed alcohol for 10 years. Abstinence commenced in March 1995 and his Clinical Institute Withdrawal Assessment for Alcohol, Revised (CIWA-Ar) score4 was 20. One week later, he had a convulsion during sleep, which persisted for 30 seconds. He reached the emergency room 30 minutes after the seizure and regained consciousness on arrival. Neurological examination revealed anterograde amnesia. Abnormal laboratory tests were serum K 3.3 mEq/L, leucocyte count 11 000/mm3, aspartate aminotransferase (AST) 120 U/L, glutamine aminotransferase (ALT) 100 U/L, c-glutamyl transpeptidase (gGT) 110 U/mL and creatinine phosphokinase (CPK) 375 IU/mL. Cranial CT revealed atrophy of the vermis only. However, flaccid paraparesis (MRC grade 0) and areflexia at the knee and ankle of both legs developed acutely one hour after the convulsion. Serum K had dropped to 2.4 mEq/L and the TTKG was 1.8. Propranolol and potassium chloride were administered. Three hours later, his serum K had increased to 3.1 mEq/L and motor strength and tendon reflexes recovered. Phenytoin 300 mg/day was commenced and the serum level was maintained in the therapeutic range at 8–11 lg/mL. During 4 years follow-up, he had several tonic–clonic convulsions, commencing 3 months after the first seizure but without hypokalemia or paralysis. He did not consume alcohol again but died of acute myocardial infarct in 1999. Autopsy was not done. 3.2. Case 2 This 34-year-old man had consumed alcohol for 2 years. Abstinence commenced in May 1997 and his CIWA-Ar score was 24. Five days later, he had a convulsion, which persisted for 1 minute. He regained consciousness on the way to hospital and reached the emergency room 20 minutes after the seizure. On arrival, his neurological examination was normal. Abnormal laboratory tests were serum K
3.0 mEq/L, leucocyte count 10 200/mm3, AST 160 U/L, ALT 100 U/L, gGT 72 U/L and CPK 410 IU/mL. Cranial CT revealed no structural lesion. However, a flaccid paraparesis (MRC grade 0) and areflexia at knee and ankle of both legs developed acutely forty minutes after the convulsion. Repeat serum K was 2.2 mEq/L and the TTKG was 1.6. Propranolol 5 mg/kg was administered. Two hours later, his serum K increased to 3.0 mEq/L and motor strength and tendon reflexes recovered. Sodium valporate 500 mg/day was commence and serum levels maintained in the therapeutic range at 80–100 lg/mL. During 7 years follow-up, he has had five tonic–clonic convulsions, commencing 4 months after the first seizure, but with no hypokalemia or paralysis. He has not consumed alcohol since. 3.3. Case 3 A 32-year-old hypertensive man consumed alcohol for 3 years. Abstinence commenced in February 1995 and his CIWA-Ar score was 26. Five days later, he had a convulsion during sleep, which persisted for 1 minute. He regained consciousness on the way to hospital and reached the emergency room 30 minutes after the convulsion. On arrival, his blood pressure was 162/93 mmHg and pulse rate 137 beats/min. Neurological examination was normal. Abnormal laboratory tests were serum K 3.1 mEq/L, AST 74 U/L, ALT 88 U/L, gGT 56 U/L, CPK 225 IU/mL and lactate dehydrogenase 419 IU/mL. Cranial CT revealed no structural lesion. However, a flaccid paraparesis (MRC grade 0) with areflexia at the knee and ankle of both legs developed acutely 1 hour after the convulsion. Repeat serum K was 2.2 mEq/L and the TTKG was 1.8. Propranolol 5 mg/kg was administrated. Three hours later, his serum K had increased to 3.1 mEq/L and the motor strength and tendon reflexes recovered. Phenytoin 300 mg/day was commenced but his compliance was poor. During 4 months follow-up, he had no convulsions or paralysis. He continued to abuse alcohol and died after an episode of acute chest pain. Autopsy showed complete occlusion of coronary arteries, acute myocardial infarction and alcoholic cardiomyopathy. 4. Discussion Although 2–15% of withdrawing alcoholics develop seizures,5 and hypokalemia is not uncommon in chronic alcoholism,6 hypokalaemic paralysis is rarely reported. We aim in this report to remind clinicians of the possibility of the variable manifestations of hypokalaemia,7 and avoid its underestimation in individuals with mild symptoms or obscuration by concomitant neuropsychiatric features.8 As convulsions recurred in two of our patients without similar weakness during the follow-up period, the initial postictal hypokalemic paralysis is considered to relate to the early stages of alcohol abstinence. Three lines of evidence support a secondary rather than a primary disorder. Firstly, serum K was 2.2–2.4 mEq/L during paralysis,
W.-H. Chen et al. / Journal of Clinical Neuroscience 13 (2006) 453–456
which is usually well tolerated in cases of primary hypokalaemic paralysis. Secondly, there was no recurrence of hypokalaemia after a subsequent high carbohydrate or high calorie diet. Thirdly, there was no positive family history. Biochemical changes reflecting hypoxia and anaerobic metabolism, including acidosis, hyperlactataemia and hyperglycaemia, may be observed after convulsion.9–11 The serum K is usually normal or increases slightly in the postictal period,9,10 but may occasionally decrease due to glucose influx from glycogenogenesis.10–12 Nevertheless, symptomatic hypokalaemia or hypokalaemic paralysis is rarely reported as a complication of convulsion. Therefore, the mechanisms of excessive postictal K fluxes causing acute symptomatic hypokalemia and subsequent paralysis should be discussed. Although serum K does not usually change significantly in alcohol withdrawal or abstinence,11 there are other physiological changes, including sympathetic overactivity,10,11,13 adrenoceptor or dopaminoceptor hypersensitivity,14 hyperactive glutaminergism, downregulation of c-aminobutyric acid receptors, decreased adenosine transporter sites, an activation of the hypothalamus–pituitary–adrenal axis and increased atrial natriuretic peptide. These are usually proportional to the magnitude of the withdrawal symptoms. Sympathetic overactivity and corticoadrenal hyperactivity are common in convulsion.10,11 Both epinephrine and cortisol are potent Na+–K+ pump activators.15,16 Therefore, we propose the following explanation for the hypokalaemic paralysis in our patients. In brief, the membrane potential is maintained by the Na+–K+ pump, K leakage channel and various other Na, K and calcium channels in the resting state. Chronic alcoholism causes sympathetic activity and a downregulation of the Na+– K+ pump activity and capacity.14–16 In the early stage of alcohol abstinence, an overcompensation of Na+–K+ pump activity and sympathetic transmission occurs; the later being reflected in the moderate withdrawal reaction in our patients. Finally, the membrane Na+–K+ pump is partially activated. After a convulsion, several metabolic changes develop including hyperglycaemia, hypersecretion of epinephrine, cortisol, thyroxine and insulin, lactoacidosis from anaerobic glycolysis, and synthesis and accumulation of anionic phosphorylated compounds intracellularly.10,11 Therefore, hypokalaemia may develop via three pathways (Fig. 1): (i) activation of the membrane Na+–K+ pump by these hormones, facilitating excessive K influx; (ii) development of a co-associative influx of glucose and K; (iii) intercellular retention and accumulation of K by synthesised anionic compounds. These mechanisms initiate and sustain hypokalaemia, leading to a change in the membrane potential. The delayed onset of hypokalemia, after the seizure and within the lucid period, is probably due to the time taken for the adrenergic effect on the Na+–K+ pump, recovery of available ATPase, a sufficient accumulation of metabolic anions, or delayed hyperinsulinaemia17 or hypercortisolaemia after convulsion.
455
Fig. 1. Electrolyte and intracellular changes in the development of hypokalaemia after convulsion in our patients. An excess of epinephrine, cortisol, thyroxine and insulin activates the membrane Na+–K+ pump (1) and a co-associative influx of glucose and potassium (2) facilitates the potassium inward flow. Retention of potassium intracellularly may result from an accumulation of anionic phosphorylated compounds synthesised by anaerobic glycolysis (3).
The cause of death in alcohol abstinence depends on the duration, amount and frequency of previous alcohol consumption, as well as underlying disease, age and general health. Convulsion is an additional factor for poor outcome.5 As skeletal muscle is the largest reservoir for K haemostasis, a prolonged and excessive intracellular retention of K may enhance the development of hypokalaemia and cardiac conduction derangements, and increase fatality in this population. Patients in this study have shown a delayed development of symptomatic hypokalaemia after convulsion, particularly in the early stages of alcohol abstinence associated with a moderate withdrawal reaction. References 1. Lin SF, Hsu YD, Halperin ML. Hypokalemia and paralysis. J Med Sci 2002;22:1–12. 2. Ko GT, Chow CC, Yeung VT, Chan HH, Li JK, Cockram CS. Thyrotoxic periodic paralysis in a Chinese population. QJM 1996;89:463–8. 3. American Psychiatric Association. DSM-IV, Diagnostic and Statistical Manual of Mental Disorders. Washington DC: American Medical Association; 1994. 4. Sullivan JT, Sykora K, Schneiderman J, Naranjo CA, Sellers EM. Assessment of alcohol withdrawal: the revised Clinical Institute Withdrawal Assessment for Alcohol scale (CIWA-Ar). Brit J Addict 1989;84:1353–7. 5. Chan AWK, Lathers CM, Leestma JE. Alcohol, arrhythmias, seizures and sudden death. In: Lathers CM, Schraeder PL, editors. Epilepsy and Sudden Death. New York: Marcel Dekker Inc.; 1990. p. 329–74. 6. Elisaf M, Liberopoulos E, Bairaktari E, Siamopoulos K. Hypokalaemia in alcoholic patients. Drug Alcohol Review 2002;21:73–6. 7. Burin MR, Cook CC. Alcohol withdrawal and hypokalaemia: a case report. Alcohol Alcoholism 2000;35:188–9. 8. Reeves RR, Pendarvis EJ, Kimble R. Unrecognized medical emergencies admitted to psychiatric units. Am J Emerg Med 2000;18:390–3.
456
W.-H. Chen et al. / Journal of Clinical Neuroscience 13 (2006) 453–456
9. Orringer CE, Eustace JC, Wunsch CD, Gardner LB. Natural history of lactic acidosis after grand-mal seizures. A model for the study of an anion-gap acidosis not associated with hyperkalemia. New Engl J Med 1977;297:796–9. 10. Aminoff MJ, Simon RP, Wiedemann E. The hormonal responses to generalized tonic-clonic seizures. Brain 1984;107:569–78. 11. Meldum BS. Pathophysiology. In: Laidlaw J, Richens A, Oxley J, editors. A Textbook of Epilepsy. 3rd ed. New York: Churchill Livingstone; 1988. p. 203–35. 12. Watson WS, Lawson PM, Beattie AD. The effect of acute alcohol withdrawal on the serum potassium and total body potassium in heavy drinkers. Scot Med J 1984;29:222–6. 13. Patkar AA, Gopalakrishnan R, Naik PC, Murray HW, Vergare MJ, Marsden CA. Changes in plasma noradrenaline and serotonin levels
14.
15.
16. 17.
and craving during alcohol withdrawal. Alcohol Alcoholism 2003;38:224–31. Djouma E, Lawrence AJ. The effect of chronic ethanol consumption and withdrawal on mu-opioid and dopamine D(1) and D(2) receptor density in Fawn-Hooded rat brain. J Pharmacol Exp Therapeutics 2002;302:551–9. Nielsen OB, Harrison AP. The regulation of the Na+, K+ pump in contracting skeletal muscle. Acta Physiol Scand 1998;162: 191–200. Clausen T. Na+–K+ pump regulation and skeletal muscle contractility. Physiological Rev 2003;83:1269–324. Sweeney G, Klip A. Mechanisms and consequences of Na+, K+pump regulation by insulin and leptin. Cell Mol Biol 2001;47: 363–72.
Clinical study
Delayed hypokalemic paralysis following a convulsion due to alcohol abstinence Wei-Hsi Chen, Hsin-Ling Yin, Hung-Sheng Lin, Shun-Sheng Chen, Jia-Shou Liu
*
Department of Neurology, Chang Gung Memorial Hospital, 100 Tai Pei Road, Niao Sung Hsiang, Kaohsiung 833, Taiwan Received 16 September 2004; accepted 7 April 2005
Abstract We encountered three patients with hypokalemic paralysis following a convulsion in the early stages of alcohol abstinence. The transtubular potassium gradient was less than 2.0, suggesting intracellular potassium shift. Hypokalaemic paralysis may result from retention of intracellular cationic potassium bound by anionic phosphorylated compounds, precipitated by an acceleration of the Na+–K+ pump in alcohol withdrawal and convulsions. These findings warn of the lethal hypokalemia that may occur after convulsions, particularly soon after alcohol abstinence associated with moderate withdrawal symptoms. Ó 2006 Elsevier Ltd. All rights reserved. Keywords: Hypokalaemic paralysis; Alcohol; Convulsion; Potassium; Catecholamine
1. Introduction
2. Patients and methods
Hypokalaemic paralysis is a disorder characterized by skeletal muscle weakness due to an intracellular shift of extracellular potassium. Primary hypokalaemia is a channelopathy due to a gene mutation with an incidence of 1 in 100 000.1 However, some conditions can provoke hypokalaemic paralysis secondarily. Hyperthyroidism and hyperaldosteronism are the leading causes in Asian and Caucasian populations, respectively.2 Other causes include licorice ingestion, barium poisoning, renal tubular acidosis, diuretic abuse, Bartter syndrome, gastroenteritis and villous adenoma of the colon.1 Total body potassium does not change in primary hypokalaemic paralysis or thyrotoxic periodic paralysis, whereas in secondary disorders it is depleted via the renal or alimentary routes. Hypokalaemic paralysis has not been reported as a postictal complication previously. We report three patients with postictal hypokalemic paralysis soon after alcohol abstinence and discuss the underlying physiological mechanisms.
We treated three men with concomitant acute paraparesis and hypokalaemia following their first-ever tonic–clonic seizure, 5–7 days after alcohol abstinence. They were heavy drinkers for 2–10 years, compatible with chronic alcoholism and alcoholic dependence according to DSM-IV criteria.3 Needle electromyogram, serum potassium (K) and transtubular potassium gradient (TTKG) were performed during the paralysis, and serum K was repeated after recovery. Serum biochemistry, trace element survey, haematology, immunology, serology, toxicology (alcohol, benzodiazepine, amphetamine, heroin), urinalysis, neuroendocrinology, arterial and urine gas analysis, glucoseinsulin loading test, thyrotropin-releasing hormone test, abdominal sonography, cranial computerised tomography (CT), adrenal CT, electroencephalogram, nerve conduction studies and liver sonography were performed to investigate possible causes of the hypokalemic paralysis and to evaluate the extent of alcohol damage. Glucose-insulin loading (100 g glucose initially and 200 g again if no response) and thyrotropin-releasing hormone tests were performed 1 week after the convulsion. The formula used to determine TTKG was (Kurine/Kplasma)/(Osmurine/Osmplasma). A non-
*
Corresponding author. Tel.: +886 7 312 1101; fax: +886 7 323 4237. E-mail address: [email protected] (J.-S. Liu).
0967-5868/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.jocn.2005.04.032
454
W.-H. Chen et al. / Journal of Clinical Neuroscience 13 (2006) 453–456
renal cause is considered when TTKG is less than two, whereas a TTKG over five indicates an increased net secretion of potassium in the cortical collecting ducts (hypokalaemia). 3. Results The three men suffered a moderate alcohol withdrawal reaction after abstinence. There was no history of high carbohydrate intake, high calorie diet, or alcoholic consumption prior to the convulsion. They denied recent head injury, migraine, consumption of drugs or herbs, or a family history of seizures or paralysis. In all patients, the glucose-insulin loading test, thyrotropin-releasing hormone test, electroencephalogram and adrenal sonography and CT were normal. Liver sonography showed fatty liver and cirrhosis. Needle electromyogram showed no resting potential during paraparesis. 3.1. Case 1 This 55-year-old man had consumed alcohol for 10 years. Abstinence commenced in March 1995 and his Clinical Institute Withdrawal Assessment for Alcohol, Revised (CIWA-Ar) score4 was 20. One week later, he had a convulsion during sleep, which persisted for 30 seconds. He reached the emergency room 30 minutes after the seizure and regained consciousness on arrival. Neurological examination revealed anterograde amnesia. Abnormal laboratory tests were serum K 3.3 mEq/L, leucocyte count 11 000/mm3, aspartate aminotransferase (AST) 120 U/L, glutamine aminotransferase (ALT) 100 U/L, c-glutamyl transpeptidase (gGT) 110 U/mL and creatinine phosphokinase (CPK) 375 IU/mL. Cranial CT revealed atrophy of the vermis only. However, flaccid paraparesis (MRC grade 0) and areflexia at the knee and ankle of both legs developed acutely one hour after the convulsion. Serum K had dropped to 2.4 mEq/L and the TTKG was 1.8. Propranolol and potassium chloride were administered. Three hours later, his serum K had increased to 3.1 mEq/L and motor strength and tendon reflexes recovered. Phenytoin 300 mg/day was commenced and the serum level was maintained in the therapeutic range at 8–11 lg/mL. During 4 years follow-up, he had several tonic–clonic convulsions, commencing 3 months after the first seizure but without hypokalemia or paralysis. He did not consume alcohol again but died of acute myocardial infarct in 1999. Autopsy was not done. 3.2. Case 2 This 34-year-old man had consumed alcohol for 2 years. Abstinence commenced in May 1997 and his CIWA-Ar score was 24. Five days later, he had a convulsion, which persisted for 1 minute. He regained consciousness on the way to hospital and reached the emergency room 20 minutes after the seizure. On arrival, his neurological examination was normal. Abnormal laboratory tests were serum K
3.0 mEq/L, leucocyte count 10 200/mm3, AST 160 U/L, ALT 100 U/L, gGT 72 U/L and CPK 410 IU/mL. Cranial CT revealed no structural lesion. However, a flaccid paraparesis (MRC grade 0) and areflexia at knee and ankle of both legs developed acutely forty minutes after the convulsion. Repeat serum K was 2.2 mEq/L and the TTKG was 1.6. Propranolol 5 mg/kg was administered. Two hours later, his serum K increased to 3.0 mEq/L and motor strength and tendon reflexes recovered. Sodium valporate 500 mg/day was commence and serum levels maintained in the therapeutic range at 80–100 lg/mL. During 7 years follow-up, he has had five tonic–clonic convulsions, commencing 4 months after the first seizure, but with no hypokalemia or paralysis. He has not consumed alcohol since. 3.3. Case 3 A 32-year-old hypertensive man consumed alcohol for 3 years. Abstinence commenced in February 1995 and his CIWA-Ar score was 26. Five days later, he had a convulsion during sleep, which persisted for 1 minute. He regained consciousness on the way to hospital and reached the emergency room 30 minutes after the convulsion. On arrival, his blood pressure was 162/93 mmHg and pulse rate 137 beats/min. Neurological examination was normal. Abnormal laboratory tests were serum K 3.1 mEq/L, AST 74 U/L, ALT 88 U/L, gGT 56 U/L, CPK 225 IU/mL and lactate dehydrogenase 419 IU/mL. Cranial CT revealed no structural lesion. However, a flaccid paraparesis (MRC grade 0) with areflexia at the knee and ankle of both legs developed acutely 1 hour after the convulsion. Repeat serum K was 2.2 mEq/L and the TTKG was 1.8. Propranolol 5 mg/kg was administrated. Three hours later, his serum K had increased to 3.1 mEq/L and the motor strength and tendon reflexes recovered. Phenytoin 300 mg/day was commenced but his compliance was poor. During 4 months follow-up, he had no convulsions or paralysis. He continued to abuse alcohol and died after an episode of acute chest pain. Autopsy showed complete occlusion of coronary arteries, acute myocardial infarction and alcoholic cardiomyopathy. 4. Discussion Although 2–15% of withdrawing alcoholics develop seizures,5 and hypokalemia is not uncommon in chronic alcoholism,6 hypokalaemic paralysis is rarely reported. We aim in this report to remind clinicians of the possibility of the variable manifestations of hypokalaemia,7 and avoid its underestimation in individuals with mild symptoms or obscuration by concomitant neuropsychiatric features.8 As convulsions recurred in two of our patients without similar weakness during the follow-up period, the initial postictal hypokalemic paralysis is considered to relate to the early stages of alcohol abstinence. Three lines of evidence support a secondary rather than a primary disorder. Firstly, serum K was 2.2–2.4 mEq/L during paralysis,
W.-H. Chen et al. / Journal of Clinical Neuroscience 13 (2006) 453–456
which is usually well tolerated in cases of primary hypokalaemic paralysis. Secondly, there was no recurrence of hypokalaemia after a subsequent high carbohydrate or high calorie diet. Thirdly, there was no positive family history. Biochemical changes reflecting hypoxia and anaerobic metabolism, including acidosis, hyperlactataemia and hyperglycaemia, may be observed after convulsion.9–11 The serum K is usually normal or increases slightly in the postictal period,9,10 but may occasionally decrease due to glucose influx from glycogenogenesis.10–12 Nevertheless, symptomatic hypokalaemia or hypokalaemic paralysis is rarely reported as a complication of convulsion. Therefore, the mechanisms of excessive postictal K fluxes causing acute symptomatic hypokalemia and subsequent paralysis should be discussed. Although serum K does not usually change significantly in alcohol withdrawal or abstinence,11 there are other physiological changes, including sympathetic overactivity,10,11,13 adrenoceptor or dopaminoceptor hypersensitivity,14 hyperactive glutaminergism, downregulation of c-aminobutyric acid receptors, decreased adenosine transporter sites, an activation of the hypothalamus–pituitary–adrenal axis and increased atrial natriuretic peptide. These are usually proportional to the magnitude of the withdrawal symptoms. Sympathetic overactivity and corticoadrenal hyperactivity are common in convulsion.10,11 Both epinephrine and cortisol are potent Na+–K+ pump activators.15,16 Therefore, we propose the following explanation for the hypokalaemic paralysis in our patients. In brief, the membrane potential is maintained by the Na+–K+ pump, K leakage channel and various other Na, K and calcium channels in the resting state. Chronic alcoholism causes sympathetic activity and a downregulation of the Na+– K+ pump activity and capacity.14–16 In the early stage of alcohol abstinence, an overcompensation of Na+–K+ pump activity and sympathetic transmission occurs; the later being reflected in the moderate withdrawal reaction in our patients. Finally, the membrane Na+–K+ pump is partially activated. After a convulsion, several metabolic changes develop including hyperglycaemia, hypersecretion of epinephrine, cortisol, thyroxine and insulin, lactoacidosis from anaerobic glycolysis, and synthesis and accumulation of anionic phosphorylated compounds intracellularly.10,11 Therefore, hypokalaemia may develop via three pathways (Fig. 1): (i) activation of the membrane Na+–K+ pump by these hormones, facilitating excessive K influx; (ii) development of a co-associative influx of glucose and K; (iii) intercellular retention and accumulation of K by synthesised anionic compounds. These mechanisms initiate and sustain hypokalaemia, leading to a change in the membrane potential. The delayed onset of hypokalemia, after the seizure and within the lucid period, is probably due to the time taken for the adrenergic effect on the Na+–K+ pump, recovery of available ATPase, a sufficient accumulation of metabolic anions, or delayed hyperinsulinaemia17 or hypercortisolaemia after convulsion.
455
Fig. 1. Electrolyte and intracellular changes in the development of hypokalaemia after convulsion in our patients. An excess of epinephrine, cortisol, thyroxine and insulin activates the membrane Na+–K+ pump (1) and a co-associative influx of glucose and potassium (2) facilitates the potassium inward flow. Retention of potassium intracellularly may result from an accumulation of anionic phosphorylated compounds synthesised by anaerobic glycolysis (3).
The cause of death in alcohol abstinence depends on the duration, amount and frequency of previous alcohol consumption, as well as underlying disease, age and general health. Convulsion is an additional factor for poor outcome.5 As skeletal muscle is the largest reservoir for K haemostasis, a prolonged and excessive intracellular retention of K may enhance the development of hypokalaemia and cardiac conduction derangements, and increase fatality in this population. Patients in this study have shown a delayed development of symptomatic hypokalaemia after convulsion, particularly in the early stages of alcohol abstinence associated with a moderate withdrawal reaction. References 1. Lin SF, Hsu YD, Halperin ML. Hypokalemia and paralysis. J Med Sci 2002;22:1–12. 2. Ko GT, Chow CC, Yeung VT, Chan HH, Li JK, Cockram CS. Thyrotoxic periodic paralysis in a Chinese population. QJM 1996;89:463–8. 3. American Psychiatric Association. DSM-IV, Diagnostic and Statistical Manual of Mental Disorders. Washington DC: American Medical Association; 1994. 4. Sullivan JT, Sykora K, Schneiderman J, Naranjo CA, Sellers EM. Assessment of alcohol withdrawal: the revised Clinical Institute Withdrawal Assessment for Alcohol scale (CIWA-Ar). Brit J Addict 1989;84:1353–7. 5. Chan AWK, Lathers CM, Leestma JE. Alcohol, arrhythmias, seizures and sudden death. In: Lathers CM, Schraeder PL, editors. Epilepsy and Sudden Death. New York: Marcel Dekker Inc.; 1990. p. 329–74. 6. Elisaf M, Liberopoulos E, Bairaktari E, Siamopoulos K. Hypokalaemia in alcoholic patients. Drug Alcohol Review 2002;21:73–6. 7. Burin MR, Cook CC. Alcohol withdrawal and hypokalaemia: a case report. Alcohol Alcoholism 2000;35:188–9. 8. Reeves RR, Pendarvis EJ, Kimble R. Unrecognized medical emergencies admitted to psychiatric units. Am J Emerg Med 2000;18:390–3.
456
W.-H. Chen et al. / Journal of Clinical Neuroscience 13 (2006) 453–456
9. Orringer CE, Eustace JC, Wunsch CD, Gardner LB. Natural history of lactic acidosis after grand-mal seizures. A model for the study of an anion-gap acidosis not associated with hyperkalemia. New Engl J Med 1977;297:796–9. 10. Aminoff MJ, Simon RP, Wiedemann E. The hormonal responses to generalized tonic-clonic seizures. Brain 1984;107:569–78. 11. Meldum BS. Pathophysiology. In: Laidlaw J, Richens A, Oxley J, editors. A Textbook of Epilepsy. 3rd ed. New York: Churchill Livingstone; 1988. p. 203–35. 12. Watson WS, Lawson PM, Beattie AD. The effect of acute alcohol withdrawal on the serum potassium and total body potassium in heavy drinkers. Scot Med J 1984;29:222–6. 13. Patkar AA, Gopalakrishnan R, Naik PC, Murray HW, Vergare MJ, Marsden CA. Changes in plasma noradrenaline and serotonin levels
14.
15.
16. 17.
and craving during alcohol withdrawal. Alcohol Alcoholism 2003;38:224–31. Djouma E, Lawrence AJ. The effect of chronic ethanol consumption and withdrawal on mu-opioid and dopamine D(1) and D(2) receptor density in Fawn-Hooded rat brain. J Pharmacol Exp Therapeutics 2002;302:551–9. Nielsen OB, Harrison AP. The regulation of the Na+, K+ pump in contracting skeletal muscle. Acta Physiol Scand 1998;162: 191–200. Clausen T. Na+–K+ pump regulation and skeletal muscle contractility. Physiological Rev 2003;83:1269–324. Sweeney G, Klip A. Mechanisms and consequences of Na+, K+pump regulation by insulin and leptin. Cell Mol Biol 2001;47: 363–72.